Abdominal visceral fat patterning has emerged as an important predictor of glucose intolerance, dyslipoproteinemia, hypertension, and their cardiovascular complications. It is also a unique model of the prediabetic state for NIDDM. The major pathways leading to the adverse metabolic profile are linked by the coexistance of insulin resistance and adaptations in splanchnic insulin dynamics. The overall goals of this project is to continue to search to identify fundamental mechanisms which contribute to the insulin resistance and to the adaptations of splanchnic insulin dynamics in abdominal obesity and their predisposition to NIDDM. Three global specific aims and six hypotheses form the basis for this new directive. Specific Aim 1: Determine insulin-mediated regulation of capillary perfusion and its relationship to glucose metabolism and the insulin resistance of abdominal obesity. Hypothesis I.I: A rate-limiting step in insulin action is its ability to induce the redistribution of capillary flow in skeletal muscle and consequently influence the cellular mass engaged in glucose uptake and its metabolic channelling. Hypothesis 1.2: Blunted insulin-induced capillary flow redistribution, presumably due to increased alpha- adrenergic vasoreactive tone, contributes to impaired glucose metabolism and to the insulin resistance of abdominal obesity. Specific Aim 2: Evaluate the relationship of abdominal obesity with splanchnic FFA flux and hepatic insulin extraction. Hypothesis 2.1: In abdominal obesity, splanchnic FFA flux is increased as a result of diminished suppressibility of splanchnic FFA release. Hypothesis 2.2: Hepatic insulin extraction and consequently the systemic flow of insulin are regulated by the level of hepatic FFA exposure. Specific Aim 3: Determine insulin secretion pulsitilities and response dynamics and their relationships with abdominal obesity and its predisposition to NIDDM. Hypothesis 3.1: Increased insulin demand in abdominal obesity is compensated by increased insulin production, with secretory pulsitilities of normal periodicities and increased pulse amplitudes. Hypothesis 3.2: In genetically predisposed individuals, an additional defect in beta cell secretion perpetuates disruption of the secretory pulsitilities and the relative decline in insulin production. State of art techniques and thorough clinical investigations are used to fulfill these goals, Understanding of biologic mechanisms underlying the adverse metabolic profile and predisposition to NIDDM in abdominally obese women is likely to evolve.